1. Field of the Invention
This invention relates to a method for the treatment of ophthalmic diseases originating from or associated with inflammation.
2. Related Disclosure
Many ophthalmic diseases are ocular disorders which are either caused or associated with painful inflammatory complications. Such complications very often lead to an impairment of the eyesight or blindness. Among those considered most dangerous belong glaucoma, cystoid macular edema, uveitis, diabetic retinopathy, conjunctivitis and postoperational or traumatic eye inflammation. When already developed all these ophthalmic diseases may be in acute, subacute or chronic form. The causes of ophthalmic inflammatory disorders may vary from bacterial, viral, fungal, parasitic, toxic, chemical, mechanical, irritative to allergic.
Glaucoma is a group of ocular diseases with the common features of abnormally elevated intraocular pressure which slowly causes progressive loss of peripheral visual fields and then untreated, it causes a loss of central vision and ultimate blindness. The causes of the development of glaucoma are unknown. Glaucoma is usually treated topically by agents which contract the eye pupil such as pilocarpine or carbachol, systemically by osmotic agents or carbonic anhydrase inhibitors, or radically by surgery. The Merck Manual, 13th Ed., 1702, (1977).
Cystoid macular edema is a retinal edema which may result from cataract removal. A newly proposed theory of the cause of a cystoid muscular edema is a release of prostaglandins or other inflammatory mediators derived from a disrupted blood-aqueous barrier into the aqueous. This theory is supported by findings that it is possible to subdue cystoid macular edema by the pre- and/or post-operative application of topical indomethacin, known suppressant of elevated levels of prostaglandins. Albrecht v. Graefes Arch. Klin. Exp. Ophthal., 209:83-88, (1978).
Uveitis is an inflammation of the uveal tract encompassing inflammation of the iris, ciliary body and choroid. Uveitis may also develop following trauma where the ciliary body was injured. Predominant objective of the treatment of uveitis is suppression of damaging inflammatory activity. Dexamethazone drops, short-term systemic corticosteroid treatment or photocoagulation of the lesions are most commonly used for the treatment of uveitis. The Merck Manual, 13th Ed., 1697, (1977).
Diabetic retinopathy is microcirculatory complication associated with progressive form of the diabetes mellitus. It is characterized by proliferative neovascularization in the posterior pole of the eye often extending into vitreous cavity with subsequent vitreous hemorrhages, fibrous formation, and secondary retinal detachment and thickening of the capillary basement membrane. Treatments used to relieve severe symptoms of diabetic retinopathy include the strict control of blood pressure or laser photocoagulation of proliferating neovascular tufts to reduce the degree of retinal edema and the frequency and severity of hemorrhagic episode. The Merck Manual, 13th Ed., page 1700, (1977). In the pending application Ser. No. 162,355 applicants Ringold and Waterbury propose the systemic use of analgesics and non-hormonal anti-inflammatories in treatment of microvascular diseases.
Conjunctivitis is an inflammation of the conjunctiva and a mucous membrane characterized by a cellular infiltration and exudation. Conjunctivitis may be either acute, where the conjunctival inflammation is caused by viruses, allergy or bacteria; or chronic, where the inflammation of the conjunctiva is characterized by exacerbations and remissions that occur over the period of months or years. The causes for chronic conjunctivitis are similar to those of acute conjunctivitis. The treatment of both acute and chronic conjunctivitis include the topical administration of sulfonamide drops, antibiotic ointments, or systemic antibiotic therapy. The most important prevention of chronic conjunctivitis is elimination of all irritating factors. In the case of allergic conjunctivitis, topical corticosteroid therapy is also indicated. Merck Manual 13th Ed., page 1687 (1977).
Other inflammatory complications of the eye are those developing after the direct injury to the dye or those caused by trauma during the eye surgery. Injuries to the eye may be caused by foreign bodies, lacerations, contusions, burns by chemicals, or others. The treatment of eye injuries and post-traumatic inflammations consists of anesthesia, precise diagnosis of the injury or trauma and post-traumatic or pre- or post-operative prevention of development of inflammation. The Merck Manual, 13th Ed., page 1680 (1977).
Compounds which are subject of this invention and those having similar structures to these compounds are known and have been described in U.S. Pat. Nos. 4,089,969; 4,232,038; 4,087,539 and 4,097,579. They are generally useful as a systemic anti-inflammatory, systemic analgesic and systemic antipyretic agents and smooth muscle relaxants. Their proposed uses as anti-inflammatories, antipyretics, analgesics or as a smooth muscle relaxants are in the form of tablets, capsules, suppositories, oral suspensions for systemic pediatric use or as a powdered top dressings for veterinary use. These compounds were not previously administered topically, i.e., directly to the eye, to prevent or treat ophthalmic diseases probably because their non-irritating properties are unexpected and surprising.